Molecular docking and ADME studies of natural compounds against bitter taste receptors( TAS۲Rs )

A subfamily of ۲۵ G protein-coupled receptors called the human bitter taste receptors (TAS۲Rs) mediates the perception of the bitter taste. The three TAS۲Rs (TAS۲R۱۴, TAS۲R۳۹, and TAS۲R۴۶) stand out from the rest of the TAS۲Rs. Since they are the most widely tuned bitter ness receptors, recognize a wide range of chemical, natural, and miscellaneous agonists and antagonists in the micromolar range with extremely low potency. In addition, the receptors are expressed in oral, and several extra-oral tissues, and they are suggested for having salient physiological roles associated with innate immune responses, cancer, and male fertility. In the present study, computational techniques (molecular docking, in silico ADMET, and predication of drug-likeness) were used to perform virtual screening on ۴۵۲ natural ligands selected from the bitterDB database. Studies on receptor-ligand binding were carried out by Schrodinger drug discovery Suite. Subsequently, the Glide docking program and extra precision (XP) were applied. The best ligands based on docking score are myricetin(-۱۱.۵۰Kcal/mol), dihydrofisetin (-۹.۳۳Kcal/mol), and artesin(-۹.۱۹Kcal/mol) for TAS۲R۱۴, TAS۲R۳۹, and TAS۲R۴۶ receptors, respectively. The docking results depict the promising potent natural product which can interact with the TAS۲Rs receptor for therapeutic approaches. Furthermore, higher potency ligands are needed to investigate the mentioned three receptors function and to modulate them for future clinical applications, such as cancer treatment or taste prediction.

کلیدواژه ها:

Bitter Taste Receptor ، Molecular Docking ، Natural Compound